To discuss what inspection readiness entails, I invited Donna Dorozinsky, Founder & CEO of Just in Time GCP to the show.
Donna is a business consultant who has over 30 years of experience in study operations that includes clinical operations, safety, data management, biostatistics, clinical supply management, and TMF management.
Her vast experiences dealing with small to large pharmaceutical companies, academic centers, regulatory agencies, clinical research organizations, and investigator sites provides her with the knowledge to assist research organizations in all areas of clinical compliance.
Donna has presented training programs in topics of GCP compliance, Quality Management Systems, Inspection Readiness, and Trial Master File (TMF) Management.
She is the Lead Editor in the newest edition of Good Clinical Practice: A Question and Answer Guide 2024/2025, is a member of the TMF Reference Model Steering Committee, and was recently named an Ernst & Young Entrepreneur of the Year.
Donna earned a Bachelor of Science in Nursing from Gwynedd Mercy University where she is currently serving as a member of the Board of Trustees and a Master of Science in Nursing from Widener University.
Please join me in welcoming Donna Dorozinsky on the Clinical Trial Podcast.
Sponsor(s):
This podcast is brought to you by Florence Healthcare. Florence eliminates chaotic workflows in clinical research operations with remote access and digital workflow platforms. More than 37,000 study sites, sponsors, and CROs in 90 countries trust them to accelerate their operations. To learn more, visit https://florencehc.com
This podcast is brought to you by Calyx. Calyx is a trusted name in medical imaging, having delivered imaging services to meet the needs of global biopharmaceutical sponsors and clinical research organizations for over 25 years. To learn more, visit https://www.calyx.ai/
SELECTED LINKS FROM THE EPISODE:
Connect with Donna Dorozinsky
Company: Just in Time GCP
Book: Good Clinical Practice: A Question & Answer Reference Guide 2024-2025
FDA Good Clinical Practice (GCP) E6(R3)
FDA Clinical Trial Guidance DocumentsQuality Management Systems
Medical and Health Product Regulatory Agency (MHRA)
Standard Operating Procedures (SOPs)
Institutional Review Board (IRB)
Bioresearch Monitoring Program (BIMO) Compliance Programs
Pharmaceutical and Medical Device Agency (PMDA)
Trial Master File Reference Model
FDA – Health Canada – MHRA Good Clinical Practice and Pharmacovigilance Compliance Symposium (YouTube)
Show Notes:
- [0:20] Donna Dorozinsky’s ackground
[2:47] Sponsor Message: Florence Healthcare https://florencehc.com
[4:00] Donna Joins the show and Discusses her Recent Publication
- Originally used book in early 2000s
- Barnett was developing a new edition in 2016-2018 wanting to add a chapter on Trial Master Files
- Built a relationship with new editor and wanted to bring a perspective that wasn’t US centric
- Inspired partly by COVID Pandemic and move towards decentralized clinical trials
[7:22] Current State of GCP
- Tencellerate has done a really good job setting core curriculum for investigator site training
- Movement towards making GCP Training fun and relatable
- Important to pick training that aligns with your area of expertise
[9:18] Is Just GCP Enough or Should the Sponsor be also Doing Additional Training?
- New vs experienced investigators have different understandings of GCP and should have different training approaches
- Site Initiation Visit (SIV) should incorporate GCP training
[10:57] What Other Guidance Documents are Helpful in Learning GCP?
- ICH E6 R3 Draft revision is really good to reference
- Guidances around electronic records are helpful
- FDA GCP Guidance document most important to review
[12:15] What is Inspection Readiness and Why is it Important
- Inspection Readiness is a steady state of operation
- Inspection Ready means you have all the evidence to show the quality conduct of the study and documentation is filed in your TMF based on milestones of your study
- Readiness is relative to where the study is currently in operation. It is reasonable to not have certain activities done if a study is still ongoing
- What you say you’re going to do, what you did, and the documentation to support it
[15:06] What is the Process Like to Get Inspection Ready?
- Mock Inspections and workshops to prepare for them are helpful
- Mock inspections need to be done at a time that is sensible to the current study status
- Workshopping requires understanding the study plan and the documentation used during the study
- Look for discrepancies between SOPs and what is documented in the TMF
- Make sure there is alignment between Sponsor, IRB and CRO
[18:22] What are Common Focus Items for FDA Inspectors?
- Check Box Inspections: standardized inspections that align with routine procedures
- Issue Driven Inspections: inspections driven issues identified with a sponsor or study
- Historical Inspections: Inspections driven because of past findings from other inspections. Checking to see if improvements have been made
[20:59] How Do We Prepare for Potential Site Inspections?
- Understand what’s in the TMF
- Coach staff on how to respond to a potential issue
- Be a collaborative partner
[22:52] Common Findings or Observations During Regulatory Inspections
- FDA, MHRA, and EMA publish annually and are usually two years behind most common findings
- Doesn’t change much year to year. Data integrity, protocol compliance, and oversight are huge factors
- Robust process for protocol deviations are best practice
- Ensure monitoring reports are done with quality
[25:50] Sponsor Message: Florence Heatlhcare (https://florencehc.com/) & Calyx (calyx.ai)
[28:31] Best Practices for Correcting or Preventing Inspection Findings
- Memos should be a last resort
- Good oversight throughout a study process helps to prevent findings
- Honestly is the best policy during inspections. Explain what part of the study was done poorly at start of inspection
[30:42] Differences between FDA, EMEA or MHRA Inspections
- FDA can be unpredictable which makes preparing for them difficult
- EMA/MHRA want access prior to the inspection and usually 3 months after the inspection.
[32:25] Donna’s TMF Provider Recommendations
- Generally vendor agnostic on TMF services
- Try to avoid making recommendations to change TMF during inspections or audit prep
- Important for sponsors to pick a TMF that fits their use case and size
[35:09] Using Tools that are not Static for Clinical Research
- SharePoint or Dropbox sometimes used in place of a TMF management system for small companies
- Need systems to be validated
- Not typically a first choice because they’re not designed with TMF functionality in mind
- Access control and management in these systems can be a challenge
[38:01] Managing Inspection Anxiety Among Staff Members
- Confidence comes from practice
- Have the mock inspections focus on the areas that you want to practice so when the real inspection comes it feels routine
- Managing pressure and anxiety are a huge factor
- Make it “just another day at the office”
[40:22] Working Within the GCP Framework to Conduct Registry Studies
- Guidances coming out from different health authorities
- TMF Reference Model actually came from a structure for a real world study
- Regulators need to take into account all the various ways we manage a clinical trial.
- Focus on oversight and quality
[42:29] GCP, Digital Technology, and Decentralized Trials
- Harder to control with decentralized trials
- Training quality can vary for sites in decentralized studies
- Site and vendor selection is really important for these studies
[45:47] Donna’s Recommended Resources, Media, and Conferences
- Donna’s book
- FDA/MHRA and Health Canada from 2025 on GCP
- Home Team – Adam Sandler
- Mighty Ducks
[49:51] Sponsor Message: Calyx (calyx.ai)
Major Themes:
- “Inspection Readiness” is a stable state of operation and is one that is achieved through good organizational practices and an effective SOP structure. Being inspection ready means you have all the evidence to show the quality conduct of the study and documentation is filed in your TMF based on the milestone of your study
- Mock inspections are a helpful exercise, but it is important to be strategic about when you conduct them. When deciding to do a mock inspection, consider the state of the studies that will be inspected and what you can learn from the exercise. Much of the value of mock inspection comes from reducing the anxiety for inspection days and giving people facing inspection staff confidence.
- Inspection approaches can vary depending on which regulatory agency is conducting them. The FDA and MHRA/EMA vary in their approaches to conducting inspections. These agencies provide annual reporting on inspection findings; these can provide important insights it what aspects of research practices can be improved
Quotes:
- The FDA, MHRA and EMA are forced on data integrity. They’re focused on oversight, a huge focus on oversight these last couple of years, protocol compliance. It’s one thing that I don’t know that sponsors spend enough time managing.
- I think that maintaining a non-threatening environment through preparation is a really good way to minimize inspection anxiety. A little bit of anxiety when you have to perform is never a bad thing, but anxiety that immobilizes you is a really bad thing.
- A trial master file that’s inspection ready means that you have all of the evidence to show the quality conduct of the study, and that documentation is filed in your trial master file based on the milestones of your study.
Audience Questions:
Do regulatory inspections make you anxious? Have you ever helped to support a regulatory inspection?
